The present invention relates to a unique class of polypeptides which are potential antagonists for insulin in that they possess binding affinity for insulin and share apparent commonality of structure with the cellular insulin receptor binding site. In addition, the invention is directed to antibodies raised against these novel peptides which have potential diagnostic and therapeutic utility in determining the levels of insulin receptor expression and in agonizing or antagonizing the hormonal effects of insulin, respectively.
Hyperinsulinemia is a condition relating to overproduction of insulin by, for example, hyperplastic or neoplastic pancreatic B cells. This condition may also result from the parenteral overdosage of insulin to a diabetic patient. In any case, hyperinsulinemia may result in diverse and unwanted physiological effects such as disturbance of carbohydrate metabolism possibly resulting in convulsions and coma. While treatments exist for the elevation of acutely low glucose levels resulting from hyperinsulinemia, the present invention includes a method for the rapid deactivation of circulating blood insulin.
The maintenance of an appropriate insulin level is an important aim in the control of diabetics melitis. While methods for the monitoring of circulating insulin levels are available, they tend to be cumbersome and overly expensive. One advantage of the present invention is that it comprises a relatively simple, sensitive and accurate method for monitoring blood insulin levels.
An improved probe specific for the cellular insulin receptor is also inherently an advantage resulting from application of the present invention. Antibodies directed toward the polypeptides of the present invention may be used to locate, quantitate, separate or isolate cellular insulin receptor or insulin-binding components thereof.
While exact binding site for insulin on the insulin receptor is unknown, insulin has been described as having a receptor-binding domain which includes amino acid residues 22-27 of the insulin B-chain (Blundell et al. Nature, Vol. 257, pp. 197-203, Sept. 18, 1975) These residues are invariant in most mammalian insulin molecules. The nucleic acid sequence coding for human and other mammalian insulins has been reported (Bell et al., Nature, Vol. 295, pp 31-35, Jan. 7, 1982).